Exosomal LncRNA TM7SF3-AU1 Aggravates White Matter Injury via MiR-702-3p/SARM1 Signaling After Subarachnoid Hemorrhage in Rats

作者全名："Zhang, Zhaosi; Yan, Jin; Chen, Hong; Zhao, Guosheng; Liu, Liu; He, Junchi; Xia, Xiangping; Zhou, Chao; Sun, Xiaochuan"

作者地址："[Zhang, Zhaosi; Yan, Jin; Chen, Hong; He, Junchi; Zhou, Chao; Sun, Xiaochuan] Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing, Peoples R China; [Zhao, Guosheng] Chongqing Med Univ, Affiliated Hosp 2, Dept Orthoped, Chongqing, Peoples R China; [Liu, Liu] Chongqing Univ, Ctr Hosp, Chongqing Emergency Ctr, Dept Neurosurg, Chongqing, Peoples R China; [Xia, Xiangping] Zunyi Med Univ, Affiliated Hosp, Dept Neurosurg, Zunyi, Guizhou, Peoples R China"

通信作者："Sun, XC (通讯作者)，Chongqing Med Univ, Affiliated Hosp 1, Dept Neurosurg, Chongqing, Peoples R China."

来源：MOLECULAR NEUROBIOLOGY

ESI学科分类：NEUROSCIENCE & BEHAVIOR

WOS号：WOS:001129680900001

JCR分区：Q1

影响因子：5.1

年份：2023

卷号：　

期号：　

开始页：　

结束页：　

文献类型：Article; Early Access

关键词：Subarachnoid hemorrhage; Exosomes; White matter injury; LncRNA TM7SF3-AU1; MiR-702-3p; SARM1

摘要："Subarachnoid hemorrhage (SAH) is a devastating disease associated with a high mortality and morbidity. Exosomes have been considered as a potential therapeutic target for SAH. However, the effect of exosomes in SAH remains to be elucidated. In this study, we focused on investigating the effect of plasma exosomal lncRNA TM7SF3-AU1 in white matter injury after SAH. The SAH model was established by means of endovascular perforation. Exosomes were extracted from rat plasma samples. The expression of RNAs in the exosomes was detected by the transcriptomic microarray. Differentially expressed circRNA, lncRNA, and mRNA were obtained. The ceRNA network showed that the lncRNA TM7SF3-AU1 and miR-702-3p were closely associated with SARM1. Knocking down TM7SF3-AU1 promoted the expression of miR-702-3p and suppressed the expression of SARM1, and knocking down TM7SF3-AU1 also attenuated white matter injury after SAH. In addition, knocking down TM7SF3-AU1 improved the neurological deficits in locomotion, anxiety, learning, memory, and electrophysiological activity after SAH. Mechanistically, TM7SF3-AU1 was able to absorb miR-702-3p, which directly bind the SARM1 mRNA. Furthermore, the white matter injury attenuated by knockdown of TM7SF3-AU1 was partially reversed by the miR-702-3p antagomir in SAH rats. Taken together, this study showed that TM7SF3-AU1 acts as a sponge for miR-702-3p, reducing the inhibitory effect of miR-702-3p on SARM1, resulting in increased SARM1 expression and thus leading to white matter injury after SAH. Our study provides new insights into exosome-associated white matter injury. It also highlights TM7SF3-AU1 as a potential therapeutic target for white matter injury after SAH."

基金机构：National Natural Science Foundation of China [82071397]

基金资助正文：This work was supported by National Natural Science Foundation of China (No. 82071397).